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An early detection programme for cancer of the head and neck (H&N) has been conducted from January 1991 to January 1993 in Pordenone province, north-eastern Italy, an area with very high mortality rates for cancers in those sites. 627 high-risk individuals (491 males, median age 57 years and 136 females, median age 47 years) (i.e. smokers and/or drinkers of more than a half litre of wine or equivalent per day) were referred to a research nurse by 21 general practitioners. An educational message on the health hazards of tobacco and alcohol abuse was delivered together with an invitation to undergo a free ear, nose and throat (ENT) examination at a nearby hospital. 212 individuals (34%) underwent the ENT visit. The influence of various individuals' characteristics on the lack of compliance was assessed. Female sex and absence of ENT symptoms were associated with a more than two-fold higher lack of compliance. Current smokers were more than three-fold less likely to accept the invitation to undergo the examination. Conversely, alcohol intake and, within smokers, the amount smoked seemed unimportant. This study shows that the correct identification of high-risk individuals is expensive and the compliance with a H&N cancer early detection programme relatively low, especially among smokers.

The clinical records of 207 patients with squamous cell carcinoma of the head and neck, diagnosed and surgically treated at the Otolaryngology Division of Pordenone General Hospital and Aviano Cancer Centre, northeast of Italy, from January 1982 to December 1987, were retrospectively reviewed to gather information on blood transfusions and other characteristics potentially related to survival. The group of patients (mean age = 59 years) included 85 cases (41%) of laryngeal cancer, 80 cases (39%) of oropharyngeal and hypopharyngeal cancer, and 34 cases (16%) of cancer of the oral cavity. Fifty-five patients (27%) did not receive any blood transfusion while 152 patients were transfused with different amounts of blood. At the univariate analysis, nodal involvement, clinical stage, type of therapy, status of surgical margins, and metastatic spread beyond the nodal capsule appeared to be significantly linked to prognosis. After adjustment for other prognostic variables, transfused patients showed a twofold higher hazard ratio as compared to nontransfused patients, but such an unfavorable predictive value should be evaluated in the context of the other prognostic correlates of cancer of the head and neck.

Infection from human immunodeficiency virus (HIV) is well known for the particular host susceptibility to a variety of opportunistic infections and unusual malignant neoplasms. Although no tumor develops exclusively in concomitance with HIV infection, malignancies in these patients have different clinical behaviour, response to treatment and prognosis than the pattern observed in HIV negative hosts. Kaposi's sarcoma (EKS) and non-Hodgkin's lymphoma (NHL) are tumors per se diagnostic of AIDS in patients with HIV infection. From 1987 to 1991, 210 HIV positive patients underwent ENT examination without symptom-related selection: 128 were intravenous drug users, 50 homosexual males, 22 heterosexuals, 4 intravenous male homosexual drug users, 3 blood recipients and 3 subjects without known risk factors. Sixteen were allocated in group II, 37 in III, 9 in IV A, 2 in IV B, 31 in IV C1, 37 in IV C2, 48 in IV D and 30 in IV E. Fourteen had head and neck EKS localization. All were males, with a median age of 40 of which 11/14 were homosexuals. The concomitant involvement of skin and mucosa was the most common manifestation and the palate was the most frequently affected mucosal site. Twenty-four had NHL localized within the head and neck: 21 males and 4 females with a average age of 38, 10 intravenous drug users, 9 homosexual males, 3 heterosexuals, 1 blood recipient, 1 subject without known risk factors. Extranodal localization was the most frequent characteristic while the gums were the most commonly involved site. The main characteristics of head and neck manifestations of EKS and NHL are reported with references to literature. The majority of HIV infected patients with EKS or NHL have ENT localizations, perhaps because lymphatic tissue, a HIV target, is well represented in this area and contamination by infectious agents (such as Epstein-Barr virus and cytomegalovirus, probably involved in the pathogenesis of EKS and NHL) can easily occur in the head and neck. The otolaryngologist should be aware of the various, and sometimes misleading, characteristics of these diseases.

Fifty-two consecutive patients, affected by large T2 (greater than 3 cm), T3, T4, N0, or N1 previously untreated squamous cell carcinoma of the head and neck, entered this phase I-II study. Treatment consisted of a continuous 8-day infusion on the following daily schedule: cisplatin 25 mg and bleomycin 15 mg administered for 4 and 20 hours, respectively. Technical-related toxicities were 1 case each of coagulation and displacement of the catheter and 1 case of reversible monoparesis of the contralateral arm. Drug-related relevant toxicities accounted for 4 cass of grade 3 or 4 leukopenia and 2 cases of peripheral palsy of the 7th and 12th cranial nerve, respectively. Forty-five of 50 evaluable patients obtained an objective response. In particular, 13 patients obtained a complete response, 22 a partial response greater than or equal to 75%, and 10 a partial response greater than or equal to 50%. Furthermore, 5 of 31 patients showed a complete pathologic disappearance of the tumor, whereas in 12 of 31 only a microscopic residue was found.

To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non-elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post-operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor.

From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low-dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial.

Neurotoxicity after intra-arterial administration of cisplatin, alone or in combination with other chemotherapeutic agents, is not yet well-documented. In our experience with 63 previously untreated patients with head and neck cancer, we observed four patients with cranial nerve impairment ipsilateral to the cannulated artery. The first patient has already been reported, whereas the other three are the subject of the present report. Overall, all three patients developed cranial peripheral palsy a few days after the end of intra-arterial cisplatin and after a median total dose of 200 mg (range, 160-250). The nerves involved were the 12th in the first patient, the seventh in the second, and the ninth, tenth, 11th, and 12th in the third patient. Complete recovery of the palsy was noted only in the first patient. The patient reported previously had developed a cranial nerve palsy involving the ninth, tenth, 11th, and 12th nerves of the right side. The low incidence of this toxicity (6.3% in our experience) and the very high objective remission rate achieved by the intra-arterial administration of cisplatin justify the continuation of such an approach to obtain the maximum tumor regression and to research the individual predisposing factors.

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

We tested VP 16-213 in 16 patients with advanced head and neck cancer after conventional treatments. VP 16-213 was administered orally at the dosage of 100 mg/mq for 5 consecutive days every 3 weeks. No patient achieved an objective response. Toxicity was mild. VP 16-213 given at this dose and schedule revealed no activity in pretreated patients with head and neck cancer.

Thirty-one patients with advanced, biopsy-proven squamous cell carcinoma (SCC) of the head and neck were treated with intraarterial chemotherapy (IAC) and subsequent radical surgery. Cisplatin at 25 mg/d (4 hours of infusion) and bleomycin at 15 mg/d (20 hours of infusion) were administered for 10 consecutive days. Radical surgery was performed after clinical evaluation 2 weeks later. Clinical tumor regression (total disappearance or shrinkage of the tumor mass by more than 50%) was recorded in 28 of 31 (90.3%) patients. Tumor regression was then assessed pathologically using a procedure based on examination of large serial histologic sections of the whole surgical specimen. Tumor residue was classified pathologically according to the TNM categories: RO, no residual tumor (five cases [16.1%]); R1, microscopic residual tumor (tumor residue detectable only at the microscopic level; 12 cases [38.7%]); and R2, macroscopic residual tumor (tumor mass detectable also on the fresh or fixed specimen and/or by the naked eye on the stained tissue sections; 14 cases [45.2%]). Moreover, tumor cell and/or stromal changes possibly associated with tumor regression were found in 77.4% of the cases. Metastatic lymph nodes were found in 12 cases (38.7%), and regression changes were observed in most lymph node metastases. Only standardized, prospective pathologic protocols for the analysis of whole specimens by serial sections permit the assessment of existing tumor residue. The TNM classification of pathologic tumor residue and definitions that we used appear feasible and reliable enough in evaluating postchemotherapeutic tumor regression.

Twenty-seven evaluable patients with advanced head and neck squamous carcinoma were treated with a polychemotherapeutic regimen described in 1975 by Price et al. Chemotherapy consisted of vincristine, adriamycin, bleomycin, methotrexate, 5-fluorouracil, hydroxyurea, 6-mercaptopurine and citrovorum factor administered sequentially. One complete remission, 4 partial remissions, 7 minor responses were obtained for a total of 12/77 (44%) objective responses. Toxicity was acceptable. The results obtained were not better than those observed with less complicated regimens administrable on an outpatient basis.

The authors report the final analysis of a prospective phase I-II study in 53 previously untreated patients with squamous cell carcinoma (48 patients) and other histologic classifications (5 patients) of the head and neck region. Treatment consisted of cisplatin 10 mg infused intra-arterially in a 12-hour period, twice a day for 5 to 10 days via an external infusion pump. After a rest period of 5 to 7 days treatment could be restarted, with the same schedule, until a maximal total dose of 400 mg or toxicity. Patients who received at least 200 mg of cisplatin were considered evaluable for response. In 3 patients catheterization was not performed because of technical difficulties, in 9 treatment was stopped before reaching the total dose of 200 mg, (because of catheter-related toxicity in 7 patients, drug toxicity in 1, and both toxicities in 1); therefore, the patients evaluable for response, drug toxicity and catheter toxicity were 41, 43, and 49 respectively. Overall, 8 patients (19.5%) obtained a complete response (CR) and 20 (48.8%) a partial response (PR) with an objective response rate (RR) of 68.3%. Eleven patients obtained a minor response (MR), whereas only 2 (4.8%) developed a progressive disease (PD). The figures, limited only to squamous cell carcinoma of oral cavity and oropharinx (33 patients), are as follows: CR 8 (24.2%), PR 17 (51.5%), MR 7 (21.2%), and PD 1 (3.0%) for an objective RR of 75.7%. No grade IV and only 5 grade III toxicity were observed; whereas the most frequent grade I and II drug-related toxicities were anemia, transient renal impairment, and thrombocytopenia. Catheter-related toxicity accounted for five central nervous system complications (three transient motor weaknesses, one hemiparesis, one embolism) and six local problems (one coagulation of the catheter, one displacement, and four local extravasations). Intra-arterial cisplatin is, in our experience, an effective treatment and further trials employing cisplatin combination chemotherapy are needed in order to establish the exact role of the intra-arterial approach before definitive local treatments.